SIAH2
Description
The SIAH2 (siah E3 ubiquitin protein ligase 2) is a protein-coding gene located on chromosome 3.
SIAH2 is a human gene that encodes an E3 ubiquitin-protein ligase. This enzyme is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in regulating cellular response to hypoxia. SIAH2 has been shown to interact with PEG10, Synaptophysin, PEG3, and VAV1.
SIAH2 is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It accepts ubiquitin from an E2 ubiquitin-conjugating enzyme and directly transfers it to targeted substrates. SIAH2 can act either by directly binding to substrates or by functioning as a subunit of larger E3 complexes. It triggers the ubiquitin-mediated degradation of various substrates, including proteins involved in transcription regulation (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). Additionally, SIAH2 mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. It is involved in apoptosis, tumor suppression, cell cycle, transcription, and signaling processes. SIAH2 has overlapping functions with SIAH1, but it uniquely triggers the ubiquitin-mediated degradation of TRAF2. It promotes monoubiquitination of SNCA and regulates cellular clock function by ubiquitinating the circadian transcriptional repressors NR1D1 and NR1D2, leading to their proteasomal degradation. SIAH2 also plays a role in mediating the rhythmic degradation/clearance of NR1D1 and NR1D2, contributing to their circadian profile of protein abundance. Furthermore, SIAH2 mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4. SIAH2 is also part of the Wnt signaling pathway, where it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1.
SIAH2 is also known as hSiah2.
